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  • Title: Inhibitors of L-asparagine synthetase, in vitro.
    Author: Cooney DA, Driscoll JS, Milman HA, Jayaram HN, Davis RD.
    Journal: Cancer Treat Rep; 1976 Oct; 60(10):1493-557. PubMed ID: 14784.
    Abstract:
    A systematic search has been made for inhibitors of L-asparagine synthetase (L-glutamine hydrolyzing, EC 6.3.5.4) from leukemia 5178Y/AR, a rodent neoplasm resistant to the oncolytic enzyme L-asparaginase (EC 3.5.1.1), The classes of chemicals examined in this search included substrate and product analogs, agents capable of reacting with sulfhydryl functions, and a variety of modifiers whose mechanism of interaction with proteins is known. In general, antagonists of L-glutamine and thiol reagents proved to be the most effective inhibitors of L-asparagine synthetase from this tumor source. Within these groups, certain structural prerequisites to inhibition are reported. Attempts to correlate oncolytic potency with enzyme-inhibitory potency were unsuccesful.
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